2 Taxonomy of Leishmania PhylumOrderFamilyGenusSarcomastigophoraKinetoplastidaTrypanosomatidaeLeishmania
3 Leishmania donovani ♦ Zoonotic parasite ♦ It is one of the 5 major parasitic diseases♦ It is endemic in northern to Yangtse river♦ 0.5 million patients before 1949♦ Basically eradicated in 1958
4 Morphology of Leishmania Digenetic Life Cycle1-Promasitogte*Insect stageMotileMidgut2-Amastigote*Mammalian stageNon-motileIntracellular
5 Life cycleLife cycle♦ The organism is transmitted by the bite of several species of blood-feeding sand flies (Phlebotomus) which carries the promastigote in the anterior gut and pharynx.Promastigote of Leishmania spPromastigote of Leishmania sp Promastigote of Leishmania sp
6 Life cycle♦ Promastigote gains access to mononuclear phagocytes where it transform into amastigotes and divides until the infected cell ruptures. The released organisms infect other cells.♦ Promastigote gains access to mononuclear phagocytes where it transform into amastogotes and divides until the infected cell ruptures. The released organisms infect other cells.
7 *Phlebotomus sendfly is the Life cycle♦ The sandfly acquires the organisms during the blood meal, the amastigotes transform into flagellate promastigotes and multiply in the gut until the anterior gut and pharynx are packed. Dogs and rodents are common reservoirs.*Phlebotomus sendfly is theVECTORof Leishmania
8 Clinical Disease Visceral Cutaneous Generally Self- healing Fatal (90% untreated)LiverSpleenBone marrowCutaneousGenerally Self- healingSkinMucous membranesMuco cutanousMuco cutanousmucosal involvement may occur if a skin lesion near the mouth or nose is not treated
12 Main Points of Life Cycle ♦ Host: man and sandfly♦ No sexual development in the host♦ Residing site: macrophage♦ Infective stage: promastigote♦ Infective route: inoculation of sandfly♦ Reservoir host: dog♦ Infection could also via transfusion
15 Cutaineous Leishmaniasis Clinical manifestation♦ Most common form♦ Characterized by one or more sores, papules or nodules on the skin♦ Sores can change in size and appearance over time♦ Often described as looking somewhat like a volcano with a raised edge and central craterSome sores are covered by a scab or have not yet ulcerated so they may look like red raised plaques- sometimes with dry crust/scale
16 Cutaineous Leishmaniasis Clinical manifestation ♦ Sores are usually painless but can become painful if secondarily infected♦ Swollen lymph nodes may be present near the sores (under the arm if the sores are on the arm or hand…)
17 Cutaineous Leishmaniasis Clinical manifestation ♦ Most sores develop within a few weeks of the sandfly bite, however they can appear up to months later♦ Skin sores of cutaneous leishmaniasis can heal on their own, but this can take months or even years
18 Cutaineous Leishmaniasis Clinical manifestation♦ Sores can leave significant scars and be disfiguring if they occur on the face♦ If infection is from L. tropica it can spread to contiguous mucous membranes (upper lip to nose)
19 Cutaineous leishmaniasis Causative organismL. tropicaL. majorL. aethiopicaL. mexicanaLocationMediterranean basin, AfghanistanMiddle East, W. and N. Africa, KenyaEthiopiaCentral America and Amazon.
20 Cutaineous Leishmaniasis Small, raised lesion on trunk without significant oozing or scab.Photograph provided by COL Naomi AronsonCutaineous Leishmaniasis
21 Cutaineous Leishmaniasis Multiple lesions on arm with a variety of appearances.Photograph provided by COL Naomi AronsonCutaineous Leishmaniasis
22 Cutaneous Leishmaniasis Both lesions are leishmaniasisNote the raised border and wet appearance of the sore on the back of the hand.Sores over joints are very concerning as scarring with healing can lead to limited movement of joint.Photograph provided by COL Charles OsterCutaneous Leishmaniasis
23 Cutaneous Leishmaniasis Back of hand.Note raised border and wet appearance. Patient has bacitracin ointment applied to lesion.Photograph provided by COL Naomi AronsonCutaneous Leishmaniasis
24 Cutaneous Leishmaniasis Upper Eyelid.Note the dry, crusted/scabbed appearance which is different than previous sores shown.Photograph provided by COL Naomi AronsonCutaneous Leishmaniasis
26 Visceral Leishmaniasis KALA-AZAR Most severe form of the disease, may be fatal if left untreatedUsually associated with fever, weight loss, and an enlarged spleen and liverAnemia (low RBC), leukopenia (low WBC), and thrombocytopenia (low platelets) are commonLymphadenopathy may be presentBased on our experience with Desert Storm, well nourished American soldiers generally have a less symptomatic, relatively oligoparasitic infection that was not life threatening but posed some diagnostic challenges
27 Visceral Leishmaniasis Causative organismL.donovaniiL.d.donovani L.d.infantumL.d chagasiLocationChina, India, IranSudan, Kenya, EthiopiaMediterranean regionBrazil, Colombia, Venezuela, Argentina
28 Visceral Leishmaniasis in Desert Storm The following symptoms were found in eight visceral leishmaniasis patients returning from Desert StormFevers: 6 of 8Weight loss: 2 of 8Nausea, vomiting, low-grade watery diarrhea: 2 of 8Lymphadenopathy: 2 of 8Hepatosplenomegly: 2 of 8Anemia: 3 of 8Leukopenia or thrombocytopenia: 0 of 8Elevated liver enzymes: 6 of 8No symptoms: 1 of 8Summary of the presenting symptoms of eight soldiers with visceral leishmaniasis from Desert Storm. The summary is from an New England Journal of Medicine article by COL Alan Magill and others from the Walter Reed Army Medical Center Infectious Disease Service.Magill et al, NEJM 1993:328(19)
29 Visceral Leishmaniasis ♦ Symptoms usually occur months after sandfly bite♦ Because symptoms are non-specific and often start after redeployment there is usually a delay in diagnosis♦ Visceral leishmaniasis should be considered in any CHRONIC FEVER patient returning from an endemic area.From the Desert Storm experience, would also consider visceral leishmaniasis in patients with low grade elevated temperature, chronically elevated liver function tests and mild anemia
30 ♦ Profile view of a teenage boy suffering from visceral leishmaniasis ♦ Profile view of a teenage boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly, distended abdomen and severe muscle wasting.
31 ♦ A 12-year-old boy suffering from visceral leishmaniasis ♦ A 12-year-old boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly and severe muscle wasting.
32 ♦ Jaundiced hands of a visceral leishmaniasis patient.
33 ♦ Enlarged spleen and liver in an autopsy of an infant dying of visceral leishmaniasis.
35 Mucocutaineous Leishmaniasis ♦ Occurs with Leishmania species from Central and South America♦ Very rarely associated with L. tropica which is found in the Middle East- This type occurs if a cutaneous lesion on the face spreads to involve the nose or mouth- This rare mucosal involvement may occur if a skin lesion near the mouth or nose is not treatedMuch of the destruction is from a hyperimmune reaction to the Leishmania infection. There are not many parasites in the affected tissue so confirming the diagnosis can be difficult. This form of leishmaniasis would be unusual in soldiers infected in South West Asia.
40 Diagnosis: Cutaneous Leishmaniasis Patients with any of the following findings should be referred early to avoid long term complications:Big lesions (greater than an inch in size)Many lesions (3 or more)Sores on the faceSores on the hands and feetSores over joints
42 Treatment Cutaneous and Mucocutaneous Antimony (Pentostam®, Sodium stibogluconate) is the drug of choice20 days of intravenous therapyFluconazole may decrease healing time in L. major infectionBiopsy and culture to determine species is requiredSix weeks of therapy is neededSince L tropica is of more concern in the SWA theatre (because of potential visceralizing infection, rare mucocutaneous involvement, and chronic (recidivans) skin infection) , would not advocate use of azoles routinely as there is not data to support their use in L.tropica and speciation can not be reliably made using clinical appearance.Mucocutaneous infection is treated with a longer treatment course (28 days)
43 Treatment Visceral Leishmaniasis ♦ Liposomal amphotericin-B (AmBisome®) is the drug of choice3 mg/kg per day on days 1-5, day 14 and day 21♦ Pentostam® is an alternative therapy28 days of therapy is required♦ Although AmBisome® is widely available,
44 J Med Entomol May;36(3):Sandflies (Diptera: Psychodidae) associated with epidemic cutaneous leishmaniasis in Sanliurfa, Turkey.Alptekin D, Kasap M, Luleyap U, Kasap H, Aksoy S, Wilson ML.Department of Medical Biology, Faculty of Medicine, Cukurova University, Balcali, Adana, Turkey.As part of a project to study the possible impact of environmental change on health in southeastern Turkey, we evaluated sandfly species diversity, abundance, and habitat associations in an urban area where cutaneous leishmaniasis was undergoing epidemic re-emergence. Houses and caves in and around the city of Sanliurfa, Turkey, were sampled using mechanical aspirators, sticky papers, and CDC light traps. Of 1,649 sandflies captured, including 6 Phlebotomus and 1 Sergentomyia species, nearly all were P. papatasi (Scopoli) (967) or P. sergenti Parrot (674). Sandflies were active during June-September (hot dry season), but not during January (cool rainy season). Resting phlebotomines were abundant inside houses. Houses sampled in 3 neighborhoods with a high cutaneous leishmaniasis incidence (9-65 cases per 1,000 population) had > 10 times more flies than at a comparison site where few cases (0.2 per 1,000) have been reported. Results indicated that P. sergenti or P. papatasi were the probable vectors of cutaneous leishmaniasis during this outbreak and that control of these sandflies may eliminate transmission.
46 Toxoplasmosis Agent: Toxoplasma gondii Taxonomy: Phylum Apicomplexa Distribution: WorldwideDefinitive Host: Any member of the FelidaeIntermed. Hosts: Any warm blooded animalInvertebrates: Coprophagous (“feces-eating”)Insects can be transport hosts
47 Human toxoplasmosis Inapparent or mild flu-like illness (most cases) Fetal death and mental retardation,blindness,Epilepsy…. May not manifest for years~ congenital infections/yearOcular toxoplasmosisSevere encephalitis inİmmunocompromised persons.
48 Life Stages of Toxoplasma • Tachyzoites = proliferative form in blood or CSF,acute or recurrent• Bradyzoites = lifelong “tissue cysts”, any host• Oocysts = (with sporozoites) shed in feces after completion of sexual phase in feline gut epithelium . Infectious after 48 hours or more environmental incubation.OocystsSurvive months to years despite freezing, heat, dehydrationThousands-to-millions shed per catOocysts are shed from cats for 1-2 weeks only.Only ~1% of cats are shedding oocysts at a given time
50 The only known definitive hosts for Toxoplasma gondii are members of family Felidae (domestic cats and their relatives). 1-Unsporulated oocysts are shed in the cat’s feces2- Although oocysts are usually only shed for 1-2 weeks, large numbers may be shed. Oocysts take 1-5 days to sporulate in the environment and become infective. Intermediate hosts in nature (including birds and rodents) become infected after ingesting soil, water or plant material contaminated with oocysts . 3- Oocysts transform into tachyzoites shortly after ingestion. These tachyzoites localize in neural and muscle tissue and develop into tissue cyst bradyzoites .4- Cats become infected after consuming intermediate hosts harboring tissue cysts . Cats may also become infected directly by ingestion of sporulated oocysts. Animals bred for human consumption and wild game may also become infected with tissue cysts after ingestion of sporulated oocysts in the environment . 5-Humans can become infected by any of several routes:
54 Toxoplasma gondiiTachyzoites are the motile, asexually reproducing form of the parasite. Unlike the bradyzoites, the free tachyzoites are usually efficiently cleared by the host's immune response, although some manage to infect cells and form bradyzoites, thus maintaining the infection.
55 Routes of Transmission of Toxoplasma • Foodborne (third leading cause of all types)• Waterborne• Contaminated soil• Transplacental• Organ transplants• Blood transfusion• Laboratory accidents
56 Life Stages of T.gondii in Cats Types A-E are sexualphases, all completedin feline gut epithelium.Prepatent periods:Tissue Cysts: 3-10 daysOocysts: > 18 daysTachyzoites: > 13 days
58 ♦ Accidental ingestion of contaminated cat feces. For example,accidental touching ofhands to mouth after gardening, cleaning acat’s litter box, or touching anything that hascome into contactwith cat feces.♦ Ingestion of raw or partly cooked meat,especially pork, lamb, or venison, or bytouching hands to mouth after handlingundercooked meat.
59 Sources of T. gondii exposure ♦ Contamination of knives, utensils, cuttingboards and other foods that have had contactwith raw meat.♦ Drinking water contaminated with Toxoplasma.♦ Although extremely rare, by receiving an infected organ transplant.
60 Human Risks from Cat Contact ♦ Oocysts sporulate in 48 hours+ at roomtemperatures.♦ Most cats do not leave feces on their fur for two days,so it is unlikely that humans become infected fromdirect contact with cats themselves.♦ Because cats usually exhibit no signs of illness whilepassing oocysts, it is difficult to determine when aparticular cat's feces may be infectious to people orother mammals.♦ Most adult cats will not pass oocysts ever again afterrecovering from an initial exposure to Toxoplasma.
61 Congenital Toxoplasmosis ♦ Manifestations of congenital toxoplasmosis may notbecome apparent until the second or third decade of life.♦ Serologic tests are used to diagnose acute infection inpregnant women, but false-positive tests occur frequently,therefore, serologic diagnosis must be confirmed at areference laboratory before treatment with potentially toxicdrugs should be considered.Infant girl with T.gondii hydrocephalus
62 Congenital T. gondii Infections Many false positives via some kits (8 brands)• Send to reference lab for confirmation before treatment• PCR of amniotic fluid useful for test confirmation/exclusion• Pyrimethamine & sulfonamide for positive PCR-AF tests• Spiramycin for negative PCR-AF tests
63 Toxoplasma encephalitis The most frequentcause of focal CNSinfections in AIDSpatients
64 Toxoplasma gondii and Schizophrenia E. Fuller Torrey* and Robert H. Yolken†*Stanley Medical Research Institute, Bethesda, Maryland, USA; (2003)Recent epidemiologic studies indicate that infectious agents maycontributeto some cases of schizophrenia. In animals, infection withToxoplasmagondii can alter behavior and neurotransmitter function.In humans, acuteinfection with T. gondii can produce psychoticsymptoms similar to thosedisplayed by persons with schizophrenia.Since 1953, a total of 19 studies of T. gondii antibodies in personswithschizophrenia and other severe psychiatric disorders and incontrols havebeen reported; 18 reported a higher percentage ofantibodies in theaffected persons; in 11 studies the difference wasstatistically significant.Two other studies found that exposure to cats in childhoodwas a risk factor for the development of schizophrenia.
65 ToxoplasmosisTreatment of toxoplasmosis in immunocompetent patients is usually unnecessary. In immunocompromised patients, the recommended treatment is a combination of pyrimethamine given at mg daily and trisulfapyrimidines given at 2-6 g daily, both for a month. This drug combination inhibits dihydrofolate reductase in T. gondii, preventing synthesis of DNA and protein.
66 ToxoplasmosisIn acutely infected pregnant women, the recommended treatment includes spiramycin if the fetus has not yet acquired toxoplasmosis.Spiramycin is an antibiotic that localizes to the placenta and has been shown to reduce placental infection by 60%. It does have some teratogenic effects, which must be weighed against the risk of congenital infection. If the fetus is infected, the aforementioned drug combination is administered instead of spiramycin.